The present invention relates to controlling tablet formation and more particularly to measuring, displaying, recording and utilizing the maximum force developed by a tablet press during tabletting (i.e. tablet formation), and utilizing this information to optimize tablet formation. The invention has particular, but by no means thusly limited, application to the tabletting of so-called sustained-release type formulations. As mentioned herein, maximum compression force constitutes the highest or peak force actually developed in a tabletting event.
It may be taken as known that many tabletted formulations, particularly the sustained-release dosage forms, have a dependency on hardness, regarding, for example, in vivo rate of release. It may be also taken as known that in many tabletted formulations, tablet hardness is inversely proportional to dissolution rate, disintegration rate or rate of release, i.e. harder compressed tablets have a slower dissolution rate, disintegration rate or rate of release (hereinafter generally referred to as rate of release or release rate). It has, moreover, been determined that in certain instances there is a direct relationship between in vitro release and in vivo release.
It has been determined, that indeed, the compression force forming the tablets is linearly related to tablet hardness, and thus related to release rate, i.e. the greater the compression force used in forming a tablet, the harder that tablet will be and the slower will be the rate of release thereof, and thus in certain instances the slower the in vivo response.
It would be, therefore, highly desirable to accurately control tabletting whereby the rate of release may predictably be established within well-defined desired limits for a particular formulation, through controlling the hardness of the tablets. It is, thus, in turn, desirable that means be provided to control the compression force during tabletting, which is, as aforesaid, linearly related to hardness, and utilize said means in connection with a determination as to what compression limits correlate to the most desirable tablet response. It is, moreover, desirable to reduce the number of trials needed to establish parameter limits, as well as to ensure that the hardness chosen would not materially affect the ejection of the tablets from the press dies, and will not cause "capping" or "lamination" of the tablets.
The prior art in this field is directed to the use of tablet hardness testers to provide hardness information used for correlation to release rate. However, hardness testers can only test a limited number of tablets out of an entire batch. Moreover, they provide a particularly slow test, requiring, for example, in the area of 15 seconds per tablet. Most importantly, too, hardness testers provide a destructive test. Additionally, the hardness testers of the prior art are generally not sufficiently accurate; variations in hardness are not always detectable at the required sensitivity level. This is particularly true with regard those hardness testers which measure the force required to crush a tablet (i.e. "crush" strength) as opposed, for example, to those which measure the force required to break a tablet which is supported as a simple beam (i.e. tensile or "snap" strength), the latter having empirically been found to provide a higher measure of correlative accuracy to, for example, in vivo response. A reason for this appears to derive from the determination that as the tablets get harder, the crush strength does not appear to increase beyond a certain point, whereas the tensile strength does continue to increase, with a corresponding decrease in the rate of drug release. Although tensile or snap strength hardness testing has been shown to improve accuracy, greater accuracy is desirable and in many instances needed.
Aside from the aforementioned limitations, there are highly desirable features potentially having substantial commercial impact with are found wanting in the prior art. It would be desirable for example, to provide for instantaneous determination of maximum compression force (and therefrom hardness) for each tablet, particularly at the time of formation. It would, moreover, be highly desirable to derive a maximum compression force signal for each tabletting event free of false maximum compression force peaks. It is, of course, highly beneficial and desirable to achieve the goals herein contemplated: through non-destructive testing means; via a much faster test than that of the prior art, such as for example the hardness testers; and with an accuracy exceeding that available in the prior art. Furthermore, it is necessary for purposes of accuracy to provide that the system arrangement will not respond to false maximum compression force peaks and non-compression force peaks in the force signal (voltage) readings.